Quantitative Analysis of Thymidine Phosphorylase and Dihydropyrimidine Dehydrogenase in Renal Cell Carcinoma

Abstract

Objective: The purpose of the present study was to clarify the clinicopathological significance of both thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in renal cell carcinoma (RCC) based on a quantitative analysis of RCC patients. Methods: Levels of TP and DPD in RCC and/or uninvolved renal tissues from 65 RCC patients were measured by enzyme-linked immunosorbent assay. Results: The TP level and TP/DPD ratio were significantly higher in RCC than in adjacent uninvolved renal tissues (p < 0.0001). There was no significant difference in DPD levels between RCC and uninvolved renal tissues. The ratio of the highest to the lowest level was 623 in TP level, 28.9 in DPD level, and 985 in TP/DPD ratio. In the univariate analysis, patient’s age (p = 0.04), tumor stage (p < 0.0001), tumor size (p = 0.007), TP expression (p = 0.03), and DPD expression (p = 0.04) were significantly associated with increased risk of death. Multivariate analysis showed that patient’s age, tumor stage, and TP expression were independent prognostic factors. Conclusions: TP and DPD in RCC provide prognostic information although DPD was not an independent prognostic factor. The present finding of a wide range in these enzyme expressions in RCC suggests that a certain subpopulation with a high TP/DPD ratio has potential responsiveness to fluoropyrimidines, especially 5’-deoxy-5-fluorouridine and capecitabine.